New method matures lab-grown heart cells for better research

Researchers at the University of Toronto's Institute of Biomedical Engineering have developed a new method to mature lab-grown heart cells, so they more closely resemble adult human heart tissue. By optimizing the chemical cocktail in which these cells are grown, the team improved their structure, electrical activity and ability to contract. This advance could help create more reliable models for studying heart disease and testing new drugs, where current lab-grown cells often fall short due to their immature state.

Human stem cell-derived heart cells are widely used in research because they can model human biology without relying on animal testing. However, these cells typically behave more like fetal or newborn heart cells rather than adult ones, limiting their usefulness.

Existing approaches to improve maturation often test one or two factors at a time, but this does not account for the complex interactions between many biological signals that occur during heart development.

"This ultimately limits the use of engineered heart tissue in drug testing or in surgical grafting. Our goal was to produce a general-purpose formulation that anyone can use in their own application of stem cell-derived heart tissue."

In order to identify potential candidates for their formulation, the researchers applied a computational approach to test many combinations of nutrients, hormones and small molecules at once. Instead of evaluating each condition individually, they used an algorithm to guide experiments and identify promising combinations more efficiently. In total, they screened 169 different formulations over four iterations, selecting those that improved how cells produce and use energy, a key indicator of maturation.

This process led to the creation of a new culture medium named C16. The researchers found that heart cells grown in this solution were more mature than those grown with standard methods, showing improvements in their physical structure, beating, electrical activity and energy use.

"One of the most common reasons that a promising new medication doesn't make it to patients is that it shows signs of cardiotoxicity in clinical trials," says Callaghan.

"Animal models often aren't very reliable in predicting this cardiotoxicity, and as a result it is slower and more expensive to produce effective drugs. Ultimately, patients are left waiting. We hope that these new methods can help to improve our predictions of cardiotoxicity in pharmaceutical testing."

Beyond testing the formulation in individual cells, the researchers applied it to miniature 3D heart tissues grown in the laboratory. This platform more closely replicates the complex physical architecture of the human heart. By combining the 3D growth environment with the new nutrient formulation, the team produced lab‑grown heart tissue that beats more forcefully and exhibits greater structural organization than previous models. As a result, the tissue behaves more like a real heart, while remaining simpler to implement in standard laboratory settings than other specialized approaches.

Source:

University of Toronto Faculty of Applied Science & Engineering

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